Document Detail

Phase II clinical evaluation of doxifluridine.
MedLine Citation:
PMID:  2942245     Owner:  NLM     Status:  MEDLINE    
Disease-oriented phase II trials of doxifluridine were performed in advanced colorectal, breast, renal, endometrial, stomach, and ovarian carcinomas. The dose schedule recommended by the phase I trial (12.5 g/m2 by continuous iv infusion over 6 hours once a week for 3 weeks followed by a 1-week rest) was chosen first: the initial dose was later decreased to 10 g/m2 due to the fact that several neurotoxic effects were reported. A total of 207 patients were entered: 137 patients who received at least two courses of treatment were evaluable for response. Therapeutic activity was demonstrated in breast cancer [two complete responses (CR) and 13 partial responses (PR) among 42 patients], colon cancer (seven PRs among 35 patients), and rectal cancer (six PRs among 23 patients). Some therapeutic activity was detected in ovarian cancer (one CR among nine patients), endometrial cancer (one PR among five patients), and stomach cancer (one PR among five patients). No significant activity was noticed in renal cancer (one PR among 18 patients). Nonhematological toxicity was evaluated according to World Health Organization criteria. Nausea and vomiting were recorded in 50% of the patients (Grade 3-4 in 5%), diarrhea was recorded in 20% (Grade 3-4 in 5%), and cutaneous and allergic reactions were recorded in 10% (Grade 3-4 in 2%). Myelotoxicity during the first treatment course was mild; median wbc and platelet count nadirs (x 10(9) cells/L) were 4.1 (range, 0.1-11) and 194 (range, 20-482), respectively. Nevertheless, some cases of acute leukopenia and thrombopenia were reported. Consciousness alterations and neurologic symptoms were the major side effects (72 of 173 evaluable patients), since treatment had to be interrupted in 34 patients and four lethal neurotoxic effects occurred. At the same total dose of doxifluridine, the risk of neurotoxicity significantly increases with age and with the weekly dose and to the contrary it decreases with increasing bilirubin level. Although activity was demonstrated, this treatment cannot be recommended because of major neurotoxicity. Further pharmacological studies seem warranted to define the optimal dosage schedule and to obtain a better therapeutic index.
P Hurteloup; J P Armand; P Cappelaere; R Metz; P Kerbrat; R Keiling; P Fumoleau; P Fargeot; S Schraub; P Bastit
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer treatment reports     Volume:  70     ISSN:  0361-5960     ISO Abbreviation:  Cancer Treat Rep     Publication Date:  1986 Jun 
Date Detail:
Created Date:  1986-09-18     Completed Date:  1986-09-18     Revised Date:  2005-10-18    
Medline Journal Info:
Nlm Unique ID:  7607107     Medline TA:  Cancer Treat Rep     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  731-7     Citation Subset:  IM    
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MeSH Terms
Alopecia / chemically induced
Antineoplastic Agents / therapeutic use*
Breast Neoplasms / drug therapy
Central Nervous System Diseases / chemically induced
Colonic Neoplasms / drug therapy
Drug Evaluation
Floxuridine / adverse effects,  therapeutic use*
Heart Diseases / chemically induced
Hematologic Diseases / chemically induced
Infusions, Parenteral
Kidney Neoplasms / drug therapy
Lymphatic Metastasis
Middle Aged
Nausea / chemically induced
Neoplasms / drug therapy*,  pathology
Rectal Neoplasms / drug therapy
Reg. No./Substance:
0/Antineoplastic Agents; 3094-09-5/doxifluridine; 50-91-9/Floxuridine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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